Auraptene inhibits migration, invasion and metastatic behavior of human malignant glioblastoma cells: An in vitro and in silico study.

Objective: The present work examined the anti-metastatic effects of auraptene and their underlying mechanisms of action in U87 Glioblastoma multiforme (GBM) cells. Materials and Methods: To test the hypothesis, cell culture, Matrigel invasion assay, scratch wound healing assay, gelatin zymography assay, qRT-PCR, and western blot experiments were conducted. Results: At sublethal concentrations of 12.5 and 25 µg/ml, auraptene exhibited a significant reduction in cell invasion and migration of U87 cells, as assessed using scratch wound healing and Transwell tests, respectively. The qRT-PCR and zymography experiments demonstrated a significant decrease in both mRNA expression and activities of MMP-2 and MMP-9 following auraptene treatment. Western blot analysis also showed that MMP-2 protein level and phosphorylation of metastasis-related proteins (p-JNK and p-mTOR) decreased in auraptene-treated cells. Molecular docking studies consistently demonstrated that auraptene exhibits a significant affinity towards MMP-2/-9, the ATP binding site of mTOR and JNK1/2/3. Conclusion: Auraptene inhibited the migration and invasion of GBM cells. This inhibitory effect was induced by modulating specific mechanisms, including suppressing MMPs, JNK, and mTOR activities.

Systemic Brain Delivery of Oligonucleotide Therapeutics Enhanced by Protein Corona-Assisted DNA Cubes.

The systemic delivery of oligonucleotide therapeutics to the brain is challenging but highly desirable for the treatment of brain diseases undruggable with traditional small-molecule drugs. In this study, a set of DNA nanostructures is prepared and screened them to develop a protein corona-assisted platform for the brain delivery of oligonucleotide therapeutics. The biodistribution analysis of intravenously injected DNA nanostructures reveals that a cube-shaped DNA nanostructure (D-Cb) can penetrate the brain-blood barrier (BBB) and reach the brain tissue. The brain distribution level of D-Cb is comparable to that of other previous nanoparticles conjugated with brain-targeting ligands. Proteomic analysis of the protein corona formed on D-Cb suggests that its brain distribution is driven by endothelial receptor-targeting ligands in the protein corona, which mediate transcytosis for crossing the BBB. D-Cb is subsequently used to deliver an antisense oligonucleotide (ASO) to treat glioblastoma multiforme (GBM) in mice. While free ASO is unable to reach the brain, ASO loaded onto D-Cb is delivered efficiently to the brain tumor region, where it downregulates the target gene and exerts an anti-tumor effect on GBM. D-Cb is expected to serve as a viable platform based on protein corona formation for systemic brain delivery of oligonucleotide therapeutics.

Role of long noncoding RNAs in the regulation of alternative splicing in glioblastoma.

Glioblastoma multiforme (GBM) is a highly severe primary brain tumor. Despite extensive research, effective treatments remain elusive. Long noncoding RNAs (lncRNAs) play a significant role in both cancer and normal biology. They influence alternative splicing (AS), which is crucial in cancer. Advances in lncRNA-specific microarrays and next-generation sequencing have enhanced understanding of AS. Abnormal AS contributes to cancer invasion, metastasis, apoptosis, therapeutic resistance, and tumor development, including glioma. lncRNA-mediated AS affects several cellular signaling pathways, promoting or suppressing cancer malignancy. This review discusses the lncRNAs regulating AS in glioblastoma and their mechanisms.

Inhibition of GPR68 kills glioblastoma in zebrafish xenograft models.

OBJECTIVE: Inhibition and knockdown of GPR68 negatively affects glioblastoma cell survival in vitro by inducing ferroptosis. Herein, we aimed to demonstrate that inhibition of GPR68 reduces the survival of glioblastoma cells in vivo using two orthotopic larval xenograft models in Danio rerio, using GBM cell lines U87-MG and U138-MG. In vivo survival of the cancer cells was assessed in the setting of GPR68 inhibition or knockdown. RESULTS: In vitro, shRNA-mediated knockdown of GPR68 inhibition demonstrated potent cytotoxic effects against U87 and U138 glioblastoma cell lines. This effect was associated with increased intracellular lipid peroxidation, suggesting ferroptosis as the underlying mechanism of cell death. Translating these findings in vivo, we established a novel xenograft model in zebrafish by successfully grafting fluorescently labeled human glioblastoma cells, which were previously shown to overexpress GPR68. shRNA knockdown of GPR68 significantly reduced the viability of grafted GBM cells within this model. Additionally, treatment with ogremorphin (OGM), a highly specific small molecule inhibitor of GPR68, also reduced the viability of grafted GBM cells with limited toxicity to the developing zebrafish embryos. This study suggests that therapeutic targeting of GPR68 with small molecules like OGM represents a promising approach for the treatment of GBM.

LINC01366 and LINC01433 in Glioblastoma Multiforme: A Potential Role at the Intersection of Inflammation and Angiogenesis.

Glioblastoma multiforme (GBM) is an aggressive cancer with a poor prognosis. Inflammation and angiogenesis are important processes in GBM that are interrelated. In this study, bioinformatic investigations were performed to detect common and key genes in the inflammatory and angiogenesis pathways of GBM. Additionally, relevant long non-coding RNAs (lncRNAs) were recognized as important gene regulators. Consequently, real-time PCR and correlation analyses were used to investigate changes in gene and lncRNA expression levels and explain their relationship. RELA emerged as a common key gene in these biological processes. LINC01366 and LINC01433 were identified as putative RELA regulators in different metabolic pathways using computational assays. According to our findings, the expression levels of RELA, LINC01366 and LINC01433 were found to be significantly upregulated in GBM samples. Correlational studies revealed a significant positive relationship of gene expressions between LINC01366 and LINC01433, indicating that they may have a coordinated effect on GBM biology. Nevertheless, there was no significant correlation between these lncRNAs and RELA. The current study highlights the high expression of LINC01366 and LINC01433 in GBM and emphasizes the importance of studying lncRNAs as putative regulators in the pathophysiology of GBM. Further research is needed to clarify their specific functions, in particular the associated inflammatory and angiogenesis pathways.

Metabolic reprogramming of poly(morpho)nuclear giant cells determines glioblastoma recovery from doxorubicin-induced stress.

BACKGROUND: Multi-drug resistance of poly(morpho)nuclear giant cells (PGCs) determines their cytoprotective and generative potential in cancer ecosystems. However, mechanisms underlying the involvement of PGCs in glioblastoma multiforme (GBM) adaptation to chemotherapeutic regimes remain largely obscure. In particular, metabolic reprogramming of PGCs has not yet been considered in terms of GBM recovery from doxorubicin (DOX)-induced stress. METHODS: Long-term proteomic and metabolic cell profiling was applied to trace the phenotypic dynamics of GBM populations subjected to pulse DOX treatment in vitro, with a particular focus on PGC formation and its metabolic background. The links between metabolic reprogramming, drug resistance and drug retention capacity of PGCs were assessed, along with their significance for GBM recovery from DOX-induced stress. RESULTS: Pulse DOX treatment triggered the transient formation of PGCs, followed by the appearance of small expanding cell (SEC) clusters. Development of PGCs was accompanied by the mobilization of their metabolic proteome, transient induction of oxidative phosphorylation (OXPHOS), and differential intracellular accumulation of NADH, NADPH, and ATP. The metabolic background of PGC formation was confirmed by the attenuation of GBM recovery from DOX-induced stress following the chemical inhibition of GSK-3ß, OXPHOS, and the pentose phosphate pathway. Concurrently, the mobilization of reactive oxygen species (ROS) scavenging systems and fine-tuning of NADPH-dependent ROS production systems in PGCs was observed. These processes were accompanied by perinuclear mobilization of ABCB1 and ABCG2 transporters and DOX retention in the perinuclear PGC compartments. CONCLUSIONS: These data demonstrate the cooperative pattern of GBM recovery from DOX-induced stress and the crucial role of metabolic reprogramming of PGCs in this process. Metabolic reprogramming enhances the efficiency of self-defense systems and increases the DOX retention capacity of PGCs, potentially reducing DOX bioavailability in the proximity of SECs. Consequently, the modulation of PGC metabolism is highlighted as a potential target for intervention in glioblastoma treatment.

Comprehensive Analysis Reveals Epithelial Growth Factor Receptor as a Potential Diagnostic Biomarker in Glioblastoma Multiforme.

Glioblastoma multiforme (GBM), a highly aggressive tumor of the central nervous system, is the most common malignant brain tumor and poses a significant risk to life. GBM patients have a low survival rate owing to their aggressive nature, poor prognosis, genomic variations among patients, and histopathological differences. In this study, we used several bioinformatics platforms, namely Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN) databases, Kaplan-Meier plotter, and cBioPortal, to conduct a comprehensive analysis to highlight the expression of epithelial growth factor receptor (EGFR) in patients with GBM. Our study highlights EGFR as a potential diagnostic and prognostic marker. According to the TIMER database, EGFR was upregulated in five cancers, including GBM, head and neck squamous cell carcinoma, kidney renal cell carcinoma, kidney renal cell papillary cell carcinoma, and lung squamous cell carcinoma, whereas it was downregulated in breast invasive carcinoma, colon adenocarcinoma, pheochromocytoma and paraganglioma, prostate adenocarcinoma, rectum adenocarcinoma, and uterine corpus endometrial carcinoma. Our investigation highlighted the expression of EGFR in various clinicopathological parameters, which include age, sex, gender, and TP53 mutation status in patients with GBM. We found that EGFR was upregulated in middle-aged and older adults compared to normal tissues, while it was not significantly downregulated in young adults and older adults. EGFR was upregulated in Caucasians compared to normal tissue, whereas it was downregulated in Asian and African American populations, but this was not statistically significant. In terms of gender, EGFR was upregulated in the male population compared to the female population. Furthermore, EGFR was upregulated in patients with TP53 mutations compared to normal tissues. We also examined the correlation between EGFR gene expression and immune cell infiltration in GBM patients and the impact of EGFR mutations on patient prognosis. Our results revealed a significant positive correlation between EGFR, B cells, and macrophages, but this was not significant for other cell types. This study signified that upregulation of EGFR was associated with a poor prognosis in patients with GBM validated by the GEPIA and UALCAN databases.

Survival After Newly-Diagnosed High-Grade Glioma Surgery: What Can We Learn From the French National Healthcare Database?

BACKGROUND: This study aimed to assess the overall survival (OS) of patients after high-grade glioma (HGG) resection and to search for associated prognostic factors. METHODS: A random sample of ad hoc cases was extracted from the French medico-administrative national database, Système National des Données de Santé (SNDS). We solely considered the patients who received chemoradiotherapy with temozolomide (TMZ/RT) after HGG surgery. Statistical survival methods were implemented. RESULTS: A total of 1,438 patients who had HGG resection at 58 different institutions between 2008 and 2019 were identified. Of these, 34.8% were female, and the median age at HGG resection was 63.2 years (interquartile range [IQR], 55.6-69.4 years). Median OS was 1.69 years (95% confidence interval [CI], 1.63-1.76), i.e., 20.4 months. Median age at death was 65.5 years (IQR, 58.5-71.8). OS at 1, 2, and 5 years was 78.5% (95% CI, 76.4-80.7), 40.3% (95% CI, 37.9-43), and 11.8% (95% CI, 10.2-13.6), respectively. In the adjusted Cox regression, female gender (HR=0.71; 95% CI, 0.63-0.79; p<0.001), age at HGG surgery (HR=1.02; 95% CI, 1.02-1.03; p<0.001), TMZ treatment over 6 months after HGG surgery (HR=0.36; 95% CI, 0.32-0.4; p<0.001), bevacizumab (HR=1.22; 95% CI, 1.09-1.37; p<0.001), and redo surgery (HR=0.79; 95% CI, 0.67-0.93; p=0.005) remained significantly associated with the outcome. CONCLUSION: The SNDS is a reliable source for studying the outcome of HGG patients. OS is better in younger patient, female gender, and those who complete concomitant chemoradiotherapy. Redo surgery for HGG recurrence was also associated with prolonged survival.

Molecular imaging with 68Ga-PSMA PET/CT in high grade glioma: A biomarker for tumour neo-angiogenesis.

There are several promising radiotracers used for both staging and restaging of primary and recurrent brain tumours based on various mechanisms of tracer localization in tumour cells. 68Ga-PSMA PET has extremely low background uptake in normal brain tissue and consequently high tumour-to-brain ratio making it a promising imaging radiotracer for gliomas. 68Ga-PSMA demonstrates utility in evaluating high grade glioma during both initial workup or when suspecting recurrence. Herein the authors evaluate the role of this imaging modality and the potential future it holds in the management of high grade gliomas.

Deguelin inhibits the glioblastoma progression through suppressing CCL2/NFκB signaling pathway.

Glioblastoma multiforme (GBM) is the most common primary intracranial tumor with characteristics of high aggressiveness and poor prognosis. Deguelin, a component from the bark of Leguminosae Mundulea sericea (African plant), displays antiproliferative effects in some tumors, however, the inhibitory effect and mechanism of deguelin on GBM were still poorly understood. At first, we found that deguelin reduced the viability of GBM cells by causing cell cycle arrest in G2/M phase and inducing their apoptosis. Secondly, deguelin inhibited the migration of GBM cells. Next, RNA-seq analysis identified that CCL2 (encoding chemokine CCL2) was downregulated significantly in deguelin-treated GBM cells. As reported, CCL2 promoted the cell growth, and CCL2 was associated with regulating NFκB signaling pathway, as well as involved in modulating tumor microenvironment (TME). Furthermore, we found that deguelin inactivated CCL2/NFκB signaling pathway, and exougous CCL2 could rescue the anti-inhibitory effect of deguelin on GBM cells via upregulating NFκB. Finally, we established a syngeneic intracranial orthotopic GBM model and found that deguelin regressed the tumor growth, contributed to an anti-tumorigenic TME and inhibited angiogenesis of GBM by suppressing CCL2/NFκB in vivo. Taken together, these results suggest the anti-GBM effect of deguelin via inhibiting CCL2/NFκB pathway, which may provide a new strategy for the treatment of GBM.

Targeted Therapy with a Novel Superantigen-based Fusion Protein Against Interleukin-13 Receptor α2-overexpressing Tumor Cells: An In-silico Study.

Background & Objective: Superantigens are bacterial toxins that induce a massive immune response in the host. Superantigen staphylococcal enterotoxin B (SEB) can form a ternary complex with its receptors, MHC class II (MHCII) and TCR, and can be used in tumor-targeting therapy, particularly when cooperating with a specific vector. In this study, SEB was fused to interleukin-13 (IL13), which forms a complex with IL13 receptor α2 (IL13Rα2) overexpressed in glioblastoma multiforme (GBM) cells for therapeutic goals. Methods: We designed four fusion proteins based on the arrangement of SEB (N- or C-terminal domain) and provided a flexible inter-domain linker (no or yes), resulting in the formation of SEB-IL13, SEB-L-IL13, IL13-SEB, and IL13-L-SEB, respectively. These fusion proteins were then evaluated for their various physicochemical properties and structural characteristics. Bioinformatics tools were employed to predict, refine, and validate the three-dimensional structure of the fusion proteins. In addition, the fusion proteins were docked with IL13Rα2, MHCII, and TCR receptors through the HADDOCK 2.4 server. The candidate fusion protein was subjected to molecular dynamics simulation. Results: There were differences among the designed fusion proteins. The model with the N-terminal domain of IL13 and containing an inter-domain linker (IL13-L-SEB) was stable and had a long half-life. The docking analysis revealed that the IL13-L-SEB fusion protein had a higher binding affinity to the IL13Rα2, MHCII, and TCR receptors. Finally, using molecular dynamics simulation through iMODS, acceptable results were obtained for the IL13-L-SEB docked complexes. Conclusion: The results suggest IL13-L-SEB is a promising novel fusion protein for cancer therapeutic application.

The role of ALDH1A1 in glioblastoma proliferation and invasion.

High-grade gliomas, including glioblastoma multiforme (GBM), continue to be a leading aggressive brain tumor in adults, marked by its rapid growth and invasive nature. Aldehyde dehydrogenase 1 family, member A1 (ALDH1A1), an enzyme, plays a significant role in tumor progression, yet its function in high-grade gliomas is still poorly investigated. In this study, we evaluated ALDH1A1 levels in clinical samples of GBM. We also assessed the prognostic significance of ALDH1A1 expression in GBM and LGG (low grade glioma) patients using TCGA (The Cancer Genome Atlas) database analysis. The MTT and transwell assays were utilized to examine cell growth and the invasive capability of U87 cells, respectively. We quantitatively examined markers for cell proliferation (Ki-67 and cyclin D1) and invasion (MMP2 and 9). A Western blot test was conducted to determine the downstream signaling of ALDH1A1. We found a notable increase in ALDH1A1 expression in high-grade gliomas compared to their low-grade counterparts. U87 cells that overexpressed ALDH1A1 showed increased cell growth and invasion. We found that ALDH1A1 promotes the phosphorylation of AKT, and inhibiting AKT phosphorylation mitigates the ALDH1A1's effects on tumor growth and migration. In summary, our findings suggest ALDH1A1 as a potential therapeutic target for GBM treatment.

Role of Non-coding RNAs in the Response of Glioblastoma to Temozolomide.

Chemotherapy and radiotherapy are widely used in clinical practice across the globe as cancer treatments. Intrinsic or acquired chemoresistance poses a significant problem for medical practitioners and researchers, causing tumor recurrence and metastasis. The most dangerous kind of malignant brain tumor is called glioblastoma multiforme (GBM) that often recurs following surgery. The most often used medication for treating GBM is temozolomide chemotherapy; however, most patients eventually become resistant. Researchers are studying preclinical models that accurately reflect human disease and can be used to speed up drug development to overcome chemoresistance in GBM. Non-coding RNAs (ncRNAs) have been shown to be substantial in regulating tumor development and facilitating treatment resistance in several cancers, such as GBM. In this work, we mentioned the mechanisms of how different ncRNAs (microRNAs, long non-coding RNAs, circular RNAs) can regulate temozolomide chemosensitivity in GBM. We also address the role of these ncRNAs encapsulated inside secreted exosomes.

MicroRNA-143 overexpression enhances the chemosensitivity of A172 glioblastoma cells to carmustine.

As an aggressive malignancy, glioblastoma multiforme (GBM) is the most common type of brain tumor. The existing treatments have shown limited achievement in increasing the overall survival of patients. Therefore, identifying the key molecules involved in GBM will provide new potential therapeutic targets. Carmustine is an alkylating agent used as a supplementary therapeutic option for GBM. However, the extensive use of carmustine has been limited by uncertainty about its efficacy. MicroRNAs (miRNAs) are essential in post-transcriptional gene regulation. Many aberrantly expressed miRNAs have been detected in various types of human cancer, including GBM. In this study, we evaluated the potential therapeutic effect of miR-143 in combination with carmustine on GBM cells. A172 cells were transfected with miR-143 mimics and then treated with carmustine. To assess the cell viability, apoptosis induction, and cell cycle progression, the MTT assay, Annexin V/PI apoptosis assay, and flow cytometry were used, respectively. Furthermore, qRT-PCR assay was applied to evaluate the expression level of genes related to apoptosis. The obtained results evidenced that miR-143 transfection could promote the sensitivity of A172 cells to carmustine and enhance carmustine-induced apoptosis via modulating the expression levels of Caspase-3, Caspase-9, Bax, and Bcl-2. Also, our results revealed that combination therapy could effectively diminish cell cycle progression in A172 cells. In conclusion, these results confirmed that miR-143 could enhance carmustine-mediated suppression of cell proliferation and improve the chemosensitivity of A172 cells to this chemotherapeutic agent. Therefore, miR-143 combination therapy may be a promising GBM treatment approach.

The prognostic effect of neutrophil-to-lymphocyte ratio and De Ritis ratio in glioblastoma multiforme patients.

AIMS: Individuals with a higher De Ritis ratio (aspartate transaminase/alanine transaminase) and neutrophil-to-lymphocyte ratio (NLR) have an inferior survival in varied malignancies. To our knowledge, the prognostic potential of the De Ritis ratio and NLR to predict the survival in nonmetastatic glioblastoma multiforme (GBM) patients remains unclear. In this study, we aimed to explore the prognostic power of the De Ritis ratio and NLR in patients with nonmetastatic glioblastoma multiforme. METHODS: Data of 262 patients with glioblastoma multiforme have been retrospectively analyzed. Their age, gender, tumor characteristics, AST/ALT ratio, NLR and hemogram values, including age at diagnosis and date of diagnosis were recorded. RESULTS: The median survival time of the study group was 21 months (95% CI: 19‒23 months). The first-year and second-year survival rates were 73.0% and 40.5%, respectively. The univariate analysis revealed that the correlation of survival with age, gender, left/right location of tumor, mean platelet volume and De Ritis ratio did not reach the level of significance. The univariate analysis of the prognostic potential of NLR indicated that a 1-unit increase in NLR value translates to a 1.05 times higher risk of death (95% CI: 1.01‒1.09). CONCLUSION: The results of this study lead to the observation that NLR value can serve as an effective prognostic marker in predicting the outcomes of patients with glioblastoma multiforme. It can be positioned as an easily accessible and cost-effective biomarker for establishing appropriate therapeutic strategies (Tab. 2, Fig. 1, Ref. 20).

Hypoxia-inducible factor 1alpha and vascular endothelial growth factor in Glioblastoma Multiforme: a systematic review going beyond pathologic implications.

Glioblastoma multiforme (GBM) is an aggressive primary brain tumor characterized by extensive heterogeneity and vascular proliferation. Hypoxic conditions in the tissue microenvironment are considered a pivotal player leading tumor progression. Specifically, hypoxia is known to activate inducible factors, such as hypoxia-inducible factor 1alpha (HIF-1α), which in turn can stimulate tumor neo-angiogenesis through activation of various downward mediators, such as the vascular endothelial growth factor (VEGF). Here, we aimed to explore the role of HIF-1α/VEGF immunophenotypes alone and in combination with other prognostic markers or clinical and image analysis data, as potential biomarkers of GBM prognosis and treatment efficacy. We performed a systematic review (Medline/Embase, and Pubmed database search was completed by 16th of April 2024 by two independent teams; PRISMA 2020). We evaluated methods of immunoassays, cell viability, or animal or patient survival methods of the retrieved studies to assess unbiased data. We used inclusion criteria, such as the evaluation of GBM prognosis based on HIF-1α/VEGF expression, other biomarkers or clinical and imaging manifestations in GBM related to HIF-1α/VEGF expression, application of immunoassays for protein expression, and evaluation of the effectiveness of GBM therapeutic strategies based on HIF-1α/VEGF expression. We used exclusion criteria, such as data not reporting both HIF-1α and VEGF or prognosis. We included 50 studies investigating in total 1319 GBM human specimens, 18 different cell lines or GBM-derived stem cells, and 6 different animal models, to identify the association of HIF-1α/VEGF immunophenotypes, and with other prognostic factors, clinical and macroscopic data in GBM prognosis and therapeutic approaches. We found that increased HIF-1α/VEGF expression in GBM correlates with oncogenic factors, such as miR-210-3p, Oct4, AKT, COX-2, PDGF-C, PLDO3, M2 polarization, or ALK, leading to unfavorable survival. Reduced HIF-1α/VEGF expression correlates with FIH-1, ADNP, or STAT1 upregulation, as well as with clinical manifestations, like epileptogenicity, and a favorable prognosis of GBM. Based on our data, HIF-1α or VEGF immunophenotypes may be a useful tool to clarify MRI-PET imaging data distinguishing between GBM tumor progression and pseudoprogression. Finally, HIF-1α/VEGF immunophenotypes can reflect GBM treatment efficacy, including combined first-line treatment with histone deacetylase inhibitors, thimerosal, or an active metabolite of irinotecan, as well as STAT3 inhibitors alone, and resulting in a favorable tumor prognosis and patient survival. These data were supported by a combination of variable methods used to evaluate HIF-1α/VEGF immunophenotypes. Data limitations may include the use of less sensitive detection methods in some cases. Overall, our data support HIF-1α/VEGF's role as biomarkers of GBM prognosis and treatment efficacy.

Temozolomide (TMZ) in the Treatment of Glioblastoma Multiforme-A Literature Review and Clinical Outcomes.

Glioblastoma multiforme (GBM) is one of the most aggressive primary tumors of the central nervous system. It is associated with a very poor prognosis, with up to half of patients failing to survive the first year after diagnosis. It develops from glial tissue and belongs to the adult-type diffuse glioma group according to the WHO classification of 2021. Therapy for patients with GBM is currently based on surgical resection, radiation therapy, and chemotherapy, but despite many efforts, there has been minimal progress in tumor management. The most important chemotherapeutic agent in the treatment of this tumor is temozolomide (TMZ), a dacarbazine derivative that presents alkylating activity. It is usually administered to patients concurrently with radiation therapy after surgical resection of the tumor, which is defined as the Stupp protocol. Temozolomide demonstrates relatively good efficacy in therapy, but it could also present with several side effects. The resistance of GBM to the drug is currently the subject of work by specialists in the field of oncology, and its use in various regimens and patient groups may bring therapeutic benefits in the future. The aim of this review paper is to summarize the relevance of TMZ in the treatment of GBM based on recent reports.

Helmet Radio Frequency Phased Array Applicators Enhance Thermal Magnetic Resonance of Brain Tumors.

Thermal Magnetic Resonance (ThermalMR) integrates Magnetic Resonance Imaging (MRI) diagnostics and targeted radio-frequency (RF) heating in a single theranostic device. The requirements for MRI (magnetic field) and targeted RF heating (electric field) govern the design of ThermalMR applicators. We hypothesize that helmet RF applicators (HPA) improve the efficacy of ThermalMR of brain tumors versus an annular phased RF array (APA). An HPA was designed using eight broadband self-grounded bow-tie (SGBT) antennae plus two SGBTs placed on top of the head. An APA of 10 equally spaced SGBTs was used as a reference. Electromagnetic field (EMF) simulations were performed for a test object (phantom) and a human head model. For a clinical scenario, the head model was modified with a tumor volume obtained from a patient with glioblastoma multiforme. To assess performance, we introduced multi-target evaluation (MTE) to ensure whole-brain slice accessibility. We implemented time multiplexed vector field shaping to optimize RF excitation. Our EMF and temperature simulations demonstrate that the HPA improves performance criteria critical to MRI and enhances targeted RF and temperature focusing versus the APA. Our findings are a foundation for the experimental implementation and application of a HPA en route to ThermalMR of brain tumors.

The effects of the combination therapy of chemotherapy drugs on the fluctuations of genes involved in the TLR signaling pathway in glioblastoma multiforme therapy.

One of the most lethal and aggressive types of malignancies with a high mortality rate and poor response to treatment is glioblastoma multiforme (GBM). This means that modernizing the medications used in chemotherapy, in addition to medicines licensed for use in other illnesses and chosen using a rationale process, can be beneficial in treating this illness. Meaningly, drug combination therapy with chemical or herbal originations or implanting a drug wafer in tumors to control angiogenesis is of great importance. Importantly, the primary therapeutic hurdles in GBM are the development of angiogenesis and the blood-brain barrier (BBB), which keeps medications from getting to the tumor. This malignancy can be controlled if the drug's passage through the BBB and the VEGF (vascular endothelial growth factor), which promotes angiogenesis, are inhibited. In this way, the effect of combination therapy on the genes of different main signaling pathways like TLRs may be indicated as an impressive therapeutic strategy for treating GBM. This article aims to discuss the effects of chemotherapeutic drugs on the expression of various genes and associated translational factors involved in the TLR signaling pathway.

CENPA facilitates glioma stem cell stemness and suppress ferroptosis to accelerate glioblastoma multiforme progression by promoting GBP2 transcription.

The function of glioma stem cells (GSCs) is closely related to the progression of glioblastoma multiforme (GBM). Centromere protein A (CENPA) has been confirmed to be related to the poor prognosis of GBM patients. However, whether CENPA regulates GSCs function to mediate GBM progression is still unclear. GSCs were isolated from GBM cells. The expression of CENPA and guanylate-binding protein 2 (GBP2) was examined by quantitative real-time PCR and western blot. GSCs proliferation and stemness were assessed using EdU assay and sphere formation assay. Cell ferroptosis was evaluated by detecting related factors. The interaction between CENPA and GBP2 was analyzed by ChIP assay and dual-luciferase reporter assay. Animal experiments were conducted to measure the effect of CENPA knockdown on the tumorigenicity of GSCs in vivo. CENPA was upregulated in GBM tissues and GSCs. CENPA knockdown inhibited GSCs proliferation, stemnness, and promoted ferroptosis. GBP2 was overexpressed in GBM tissues and GSCs, and CENPA enhanced GBP2 transcription by binding to its promoter region. CENPA overexpression accelerated GSCs proliferation and stemnness and suppressed ferroptosis, while GBP2 knockdown reversed these effects. Downregulation of CENPA reduced the tumorigenicity of GSCs by decreasing GBP2 expression in vivo. In conclusion, CENPA enhanced GBP2 transcription to increase its expression, thus accelerating GSCs proliferation and stemnness and repressing ferroptosis. Our findings promote a new idea for GBM treatment.